1. Field of the Invention
This invention relates to a Tixe2x80x94Zr type alloy which possesses exceptionally high strength and yet manifests low Young""s modulus, exhibits sufficient malleability required for the use in structural members, and further excels in plastic workability.
This invention also relates to a medical appliance including a guide wire, a stent, a ventricular assisting device and a catheter which is formed of a Tixe2x80x94Zr type alloy and used for therapeutic acts under X-ray fluoroscopy represented by a percutaneous transluminal angioplasty (PTA), for example, prevailing in such a medical field as radiology, cardiovascular internal medicine and surgical medicine. More particularly, this invention relates to a medical appliance which is formed of a Tixe2x80x94Zr type alloy combining sufficient in vivo corrosion resistance, strength and workability necessary for the use in a structural material, biocompatibility, proper contrast and opaqueness, and applicability to MRI.
The Tixe2x80x94Zr type alloy of this invention comprises Ti, Zr, Nb, and Ta and, optionally such a biocompatible element as Sn, Pd, Pt, and Au, and contains no metallic elements tending to arouse anxiety about toxicity. Thus, the present invention relates to a group of Ti type alloys which is essentially possessed of safety necessary for the use in a grafting material.
These medical appliances will be explained below with reference to a stent, a guide wire, and a ventricular assisting device which are cited as examples of particularly preferable uses found therefor. The alloys mentioned above, in view of their physicochemical properties, should be understood as manifesting additional availability in medical applications and popular applications as well. The alloys ought not to be limited to those uses that are cited by way of illustration in the present specification.
2. Description of the Related Art
A Ti-based alloy excels in corrosion resistance by forming a dense oxide coating of titanium dioxide (TiO2) on the surface thereof in the open air. Owing to its various excellent properties including light weight, great strength, and high specific strength (which is the quotient resulting from the division of the tensile strength by the specific gravity), Ti-based alloys find extensive use as materials for aerospace industry, materials for chemical devices, corrosion-resistant materials for industry utilizing seawater, and materials for consumer products such as camera shutter parts, communication equipment, optical instruments, eyeglass frames, heads, faces, and shafts in wood clubs and iron clubs used in golf. Since the Ti-based alloys mentioned above are in xcex1-phase which exhibits a rigid metallic texture at room temperature, however, they admit of no easy mechanical working such as rolling, forging, or cutting, and are mechanically worked solely in their xcex2-phase region which is separated in a high temperature range and is capable of being machined under the existing circumstances. Moreover, in terms of material, they have the problem of manifesting unusually inferior workability in spite of their fine qualities as in corrosion resistance and strength as compared with other metals. This defect has inhibited conventional Ti-based alloys from finding expansion of their use in general industries.
It has been ascertained as a result of the study pursued to date that titanium (Ti), as well as zirconium (Zr), niobium (Nb), tantalum (Ta), platinum (Pt), and inorganic tin (inorganic Sn) are elements excelling in biocompatibility. They have begun to attract attention as materials for medical appliances. When they are to be used as a materials for medical appliances, however, this use requires them to manifest exacting corrosion resistance as compared with other general industrial uses. Specifically, in the use for medical appliances, since a component separated, even if in a minute amount, by elution from a given material brings adverse effects on a human body to an extent hardly deserving disregard, a material for a medical appliance is required to manifest quality of avoiding elution of a maternal component thereof via an oxide coat manifesting a passive state, even upon contacting with humor or blood. Besides the quality just mentioned above, such a fact as that a material for a medical appliance excels in affinity for the surrounding tissue and approximates closely to a Young""s modulus of a living bone constitutes itself a very important element.
For the purpose of attaining the various properties mentioned above, various Ti-based alloys have been reported to date. As typical examples of the Ti-based alloy, an alloy for the used in a dental device which comprises titanium, about 10 to 20% by weight or about 35 to 50% by weight, as the sum of a metal selected from the group consisting of niobium and tantalum, and sufficient zirconium to act as a beta stabilizer and to reduce the rate of transformation of beta structure in the alloy (WO 95/34251); and a titanium alloy containing a first metal, titanium, a second metal selected from the group consisting of zirconium and hafnium, and mixtures thereof, and a third metal selected from the group consisting of niobium, tantalum, vanadium, and mixtures thereof in a prescribed composition (WO 95/25183) may be cited. As regards the former alloy, the weight ratio of zirconium to titanium and the weight ratio of tantalum to niobium has not been referred to anywhere in the relevant official gazette. Specifically, zirconium has been described to account for a proportion of not more than 18% by weight most preferably, tantalum is referred to as accounting for a total proportion in conjunction with niobium and allowing a part of niobium to be substituted with tantalum, and the proportion of tantalum for the most preferable alloy has been stated to be zero. The alloy of this composition is deficient in malleability and proof stress, as well as in corrosion resistance which is expected to be exceptionally strong.
The latter alloy, either in the form of an oxide or on being oxidized, is allowed to form a cermet or ceramic body and is enabled to acquire an expected working efficiency by heating the alloy in a certain temperature range and oxidizing the heated alloy with an oxidant gas thereby altering the quality thereof. The alloy disclosed in WO 95/25183, however, has the problem of failing to manifest a fine beta phase at the time of forming the alloy, revealing deficiency in plasticity and workability at normal temperature, and offering inferior corrosion resistance.
Thus, the development of a Ti-based alloy which has high strength, outstanding corrosion resistance and acid resistance, easy workability, and a low Young""s modulus, particularly a Young""s modulus close to that of a living bone has been earnestly yearned for. None of the alloys perfected to date, however, satisfies all these properties.
Incidentally, medical appliances using various metals led by the Ti-based alloys have been now in use. A stent, for example, is a hollow cylindrical article which is applied to interiors of a urinary tract, a bile duct, an esophagus, and a nephric tubule as well as a blood vessel with an object of dilating a narrow intracorporeal vessel. As the materials for the stent retaining intracorporeally for a long time, stainless steel (JIS SUS316L), Ta as a pure metal, and Nixe2x80x94Ti type superelasticity alloys have been already reduced to practice.
Meanwhile, various implant grade Ti-based alloys for the use mainly in artificial joints have been studied from numerous angles. Typically, pure Ti and Ti-6Al-4V alloy (hereinafter all the compositions will be expressed in xe2x80x9cweight percentxe2x80x9d, with the balance assumed to comprise Ti and inevitable impurities, also expressed in xe2x80x9cweight percentxe2x80x9d, unless otherwise specified, in accordance with the general notation of alloy) may be cited. Various Ti-based alloys centering around the xcex2-Ti-based alloys which have been developed to date, however, have not perfectly overcome the problems of corrosion resistance and inclusion of extraneous elements. In view of these problems, attempts have been carried out to manufacture a titanium alloy using Ti, Zr, Sn, Nb, and Ta as constituent components which, as simple elements, has not been recognized to be harmful in vivo. Recently, the improvement of a Ti-based alloy has been proceeded. For example, EP-A-601,804 proposes an artificial heart and an artificial joint using a Ti-13Zr-13Nb alloy; and U.S. Pat. No. 5,888,201 proposes a self-dilating stent made of a Ti alloy using the Ti-13Zr-13Nb alloy mentioned above. Further, JP-B-08-16,256 has proposed a Ti-15Zr-4Nb-4Ta-0.2Pd alloy and a Ti-15Sn-4Nb-2Ta-0.2Pd alloy intended for the use in a long-term implanting material and U.S. Pat. No. 5,871,595 has proposed a Ti-29Nb-13Ta-4.6Zr alloy for the use as an implanting material. These alloys are characterized by containing Ti in a weight ratio of not less than 50% by weight. Further, since they are contemplated as a structural material in alloy designing, they have been awarded no due consideration about opaqueness to X-ray. For the stent which directs due consideration to the importance of contrast and opaqueness to X-ray, the provision of a radioopaque marker made of a noble metal (U.S. Pat. No. 5,725,572) and the use of a clad material formed of a noble metal and stainless steel (WO 93/19804) have been proposed. These articles use stainless steel (JIS SUS316L), primarily as the material on account of precision workability and strength. It may be concluded that these articles have not been awarded due consideration of the safety for the use as a long-term implanting material because they still have to solve the problem that the stainless steel itself is susceptible to corrosion, the problem that the plating yields to pinhole corrosion, the problem that the combination with a different metal entails galvanic corrosion, and etc.
Zr alloys, in addition to the Ti-based alloys, have been studied about the application to a medical appliance as a high biocompatible alloy. For example, U.S. Pat. No. 5,258,022 discloses an artificial cardiac valve which contains Zr as a main component thereof with regard to the blood compatibility of zirconium oxide. Recent studies and JP-A-07-188,876 disclose a Zr30Ti20Al25Pd25 alloy (atomic percent) as a Zr-based metallic glass; and JP-A-10-211,184 discloses a Zr60Al15Ni15Cu5Co5 alloy (atomic percent). These alloys are Zr-based amorphous alloys utilizing its corrosion resistance and non-magnetism. The manufacture of these amorphous alloys has been subjected to the restriction that such special methods of production as a liquid quenching method and a powder molding method should be adopted.
The titanium alloys and the zirconia alloys, as described above, respectively contain Ti and Zr as a main component in an amount of not less than 50% by weight. These alloys, on account of outstanding corrosion resistance, have been considered as an important biocompatible material and have been researched for further development. It, however, has been an universally known fact that they are deficient in workability and in cutting efficiency as compared with ordinary stainless steel. Further, since they have been designed as materials for an artificial joint and an artificial heart, they have not been awarded due consideration of contrast and opaqueness to X-ray. As regards the demands imposed in recent years on medical appliances, the popularization of a magnetic resonance imaging (MRI) apparatus has reached the point of urging the necessity of avoiding exertion of an influence on the image of MRI.
This invention, which has been initiated in view of the problems encountered by the related arts as described above, has an object of overcoming these problems.
An object of this invention, therefore, is to provide a Tixe2x80x94Zr type alloy for the use in general industry which combines high strength ("sgr"f) at normal temperature and a low Young""s modulus (E), i.e. high elasticity, and consequently excels in plasticity and workability at normal temperature, and also excels in corrosion resistance.
Another object of this invention is to provide a Tixe2x80x94Zr type alloy for the medical use which excels in plasticity, workability, and corrosion resistance at normal temperature, and also has excellent affinity with a biological tissue.
Further object of this invention is to provide, on the assumption of in vivo use and direct exposure to humor, a medical appliance formed of a novel improved Ti type alloy which exhibits high safety enough to permit protracted retention on or in the human body.
Another object of this invention is to provide a medical appliance formed of a novel improved Ti type alloy which comprises such biocompatible elements as Ti, Zr, Nb, and Ta and excludes any metallic element having a possibility of toxicity and, therefore, can provide essentially a safety necessary for a transplanting material, manifest high strength and easy workability, and excels in biocompatibility.
Yet another object of this invention is to provide a medical appliance formed of a novel Ti type alloy which exhibits a proper contrast and opaqueness to X-ray under X-ray fluoroscopy in addition to the advantages mentioned above, and particularly to provide such a medical appliance as a guide wire, a catheter, a stent, a stent graft, a venous filter, and an artificial blood vessel which demand a proper contrast and opaqueness as an added value.
Still another object of this invention is to provide a medical appliance which, in addition to the advantages as mentioned above, affects no adverse effects on an image produced in the diagnostic imaging by magnetic resonance imaging. A left ventricular assisting device in particular demands a metallic material excelling in workability because it requires to form a blood pass which is non-magnetic and excels in blood compatibility. The present object, therefore, resides in providing a metallic material satisfying these demands and a medical appliance formed of such a metallic material.
The present inventors, as a result of a diligent study pursued in search of a Tixe2x80x94Zr type alloy capable of accomplishing the objects mentioned above, have found that a Tixe2x80x94Zr type quaternary alloy formed of Ti, Zr, Nb, and Ta in a specific composition excels in plasticity and workability at normal temperature and also excels in affinity with a biological tissue. This invention has been perfected based on the knowledge mentioned above.
Specifically, the objects mentioned above can be accomplished by a Tixe2x80x94Zr type alloy which consists of 25 to 50% by weight of Ti, 25 to 60% by weight of Zr, 5 to 30% by weight of Nb, and 5 to 40% by weight of Ta, provided that the weight ratio of Zr to Ti be in the range of 0.5 to 1.5 and the weight ratio of Nb to Ta be in the range of 0.125 to 1.5.
Further, the present inventors, as the first step toward developing a medical appliance formed of a Ti type alloy having expected properties with a view to solving the problems mentioned above, have launched on the basic designing of an alloy. Both pure Ti and pure Zr are such materials as enabled to exhibit excellent corrosion resistance by forming a dense oxide coat and offer resistance to almost all chemicals. As a result of the detail study performed by the present inventors, it has been found that the corrosion resistance exhibited by pure Ti and pure Zr in various chemicals is complementary in nature. For example, pure Ti is corroded and pure Zr is hardly corroded in inorganic acids like boiling hydrochloric acid and sulfuric acid; and pure Ti is not corroded and pure Zr is corroded in inorganic chloride like an aqueous 30% by weight ferric chloride solution. The combination of the two elements, Ti and Zr, can be expected to provide an alloy having the strongest corrosion resistance. When either of Ti and Zr is adopted as a mother phase of an alloy, a possibility that the quality of either of the two elements will manifest preferentially is conceivable. From the study as mentioned above, using as a starting point a mother alloy containing mutually satisfactorily compatible Ti and Zr in nearly equal quantities, manufacturing a Tixe2x80x94Zr type alloy having suitably incorporated therein such biocompatible elements as Nb and Ta, and carefully examining the alloy with respect to physical properties and characteristics required by a relevant medical appliance such as, for example, contrast and opaqueness to X-ray, the present inventors have finally discovered a group of novel Tixe2x80x94Zr type alloys capable of attaining the objects mentioned above.
Besides the knowledge mentioned above, the present inventors have also found that Zr and Sn are suitably interchangeable in their combination with Ti. To be specific, they have found that in the alloys using Ti, Zr, Nb, and Ta in a basic composition thereof, a group of Tixe2x80x94Zr type alloys having a part of Zr substituted with Sn is similarly suitable as a material for a medical appliance. As a matter of course, such elements as H, O, N, Fe, C, Pd, Ru, and Ni which are inevitably incorporated as impurities originating in the materials of pure Ti and pure Zr can be contained in the alloy in amounts falling within a range which causes to inhibit desired properties. Specifically, industrial grade pure Ti which is used as a raw material normally contains elements in an amount of not more than 0.5% by weight, though depending on the grade of this element. Among these elements, such interstitial elements as C, N, and O which have no toxicity may be positively contained therein. In this case, as respects the ranges incapable of impairing the physical properties of the alloy, the content of each the interstitial elements and impurities does not preferably exceed 0.5% by weight. Actually, since the Tixe2x80x94Zr type alloy of this invention basically uses such non-magnetic materials as Ti, Zr, Nb, Ta, and Sn, the produced Tixe2x80x94Zr type alloy is likewise non-magnetic and the medical appliances formed thereof produce no effects on the image by magnetic resonance imaging. This quality of repelling a magnet results in imparting an important property to such a left ventricular assisting device as using magnetic force as a driving force.
The objects of this invention mentioned above can be accomplished by a medical appliance having a part which consists of 25 to 50% by weight of Ti, 25 to 60% by weight of Zr, 5 to 30% by weight of Nb, and 5 to 40% by weight of Ta, provided that the weight ratio of Zr to Ti be in the range of 0.5 to 1.5 and the weight ratio of Nb to Ta be in the range of 0.125 to 1.5.
The Tixe2x80x94Zr type alloy of this invention consists of 25 to 50% by weight of Ti, 25 to 60% by weight of Zr, 5 to 30% by weight of Nb, and 5 to 40% by weight of Ta, provided that the weight ratio of Zr to Ti be in the range of 0.5 to 1.5 and the weight ratio of Nb to Ta be in the range of 0.125 to 1.5. Since the metallic texture of the Tixe2x80x94Zr type alloy of this invention, therefore, is allowed to assume a, xcex2-phase at normal temperature without requiring any special heat-treatment in spite of using Ti and Zr as main components, the alloy manifests exceptionally fine workability fit for being rolled, cast, or mechanically processed at normal temperature and further exhibits remarkably excellent plastic workability at normal temperature. Thus, this alloy guides to a new Ti-based alloy as a material for general industry. The alloy is an optimum alloy for medical uses because all the component elements Zr, Ta, and Nb are capable of forming a dense powerful oxide coat and are excellent in in vivo affinity.
Further, a Tixe2x80x94Zr type alloy having at least either of Nb or Ta in the Tixe2x80x94Zr type quaternary alloy mentioned above substituted by at least one first substituent element selected from the group consisting of Ni, Cu, Pd, Pt, Al, Si, Cr, Mn, Co, V, Fe, Ag, Au, Sn, Mo, Hf, Zn, Ga, W, Tc, Ru, Rh, Cd, and In; and a Tixe2x80x94Zr type alloy having at least one first additive element selected from the group consisting of Ni, Cu, Pd, Pt, Al, Si, Cr, Mn, Co, O, N, V, Fe, Ag, Au, Sn, Mo, and Hf in an amount in the range of 0.01 to 5% by weight, based on the total weight of the component elements additionally incorporating therein can be used as a Tixe2x80x94Zr type alloy both for general industry and medical treatment because of their outstanding corrosion resistance and acid resistance of the mother materials and the mechanical strengths of the mother materials.
The medical appliance of this invention excels in biocompatibility and can be used as a long-term in vivo implanting material because they are formed of a novel Ti type alloy having as the main components thereof such metals as Ti, Zr, Nb, and Ta which are not harmful to a biological tissue. Further, by limiting the contents of Ti and Zr and restricting the composition ratios of Ta and Nb within specific ranges, the alloy can acquire the strongest corrosion resistance in the history and a low elasticity never attained in conventional alloys and secure high strength and workability. As a result, the medical appliance of this invention enjoys a prominent improvement of the degree of freedom in the designing. They can contribute to the enhancement of productivity and the reduction of cost concerning such medical appliances as artificial joints, artificial hearts, prosthesis, artificial blood vessels, artificial corneas, tympanic tubes, and pace makers which have been heretofore formed of Ti type materials difficult to be processed mainly on account of biocompatibility. Since the alloy of this invention is possessed of the ability to control a proper contrast and opaqueness to X-ray under X-ray fluoroscopy by properly adjusting the contents of such elements as Ta and Sn which can impart radiolucency, it can be used in a catheter, a stent, a stent graft, and a venous filter under X-ray fluoroscopy, impart proper X-ray contrast and opaqueness thereto, and provide improved medical appliances. Thus, this alloy can contribute to the therapy under the X-ray fluoroscopy so called xe2x80x9cinterventional radiologyxe2x80x9d.
In addition to the advantages mentioned above, the medical appliance of this invention brings the advantage of avoiding exertion of adverse effects on an image by MRI because it is formed of a Tixe2x80x94Zr type alloy which is composed of non-magnetic elements. That is, the medical appliance of this invention can provide such a medical appliance as an endoscopic equipment, a forceps, a surgical instrument, and a medical clip which can be used in combination with MRI. At present, the technique called as xe2x80x9cMRI interventionxe2x80x9d exists, though on the research level. This technique is a technique of conducting diagnosis and therapy by using a catheter and an endoscope under MRI relying on an image of MRI instead of X-ray, and expected to become a therapeutic technique in near future because of the merit of repressing the exposure of the technician to the X-ray. This invention can be expected to provide a medical appliance to be used in the MRI intervention and contribute greatly to the advance of medical treatment.
The above and other objects, features, and advantages of the present invention will become clear from the following description of the preferred embodiments.